缬沙坦对压力负荷心肌肥大钙调神经磷酸酶(CaN)通路的作用
Effect of Valsartan on Calcineurin Signal Pathway in Pressure Overload Induced Myocardial Hypertrophy
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摘要: 目的探讨血管紧张素Ⅱ受体(AngⅡ,AT1及AT2)拮抗剂对致心肌肥厚的钙调神经磷酸酶(CaN)信号通路的影响。方法腹主动脉缩窄法建立大鼠压力负荷模型,实验动物分为手术组(n=8);缬沙坦组(n=8):手术组+缬沙坦(1mg/kg·d);PD123319(AT2R受体拮抗剂)组(n=8):手术组+PD123319(30mg/kg·d);假手术组(n=8)。放射免疫法检测血浆、心肌AngⅡ浓度,免疫沉淀法检测心肌钙蛋白酶(ucalpain,mcalpain)及CaN蛋白表达及其磷酸化。结果缬沙坦组血浆AngⅡ浓度显著高于假手术组及PD123319组(P<0.05),缬沙坦组心肌AngⅡ浓度则低于假手术照组及PD123319组(P<0.05)。手术组ucalpain蛋白表达显著高于假手术组(P<0.01),缬沙坦组显著低于手术组及PD123319组(P<0.05),手术组与PD123319组间差异没有显著性(P>0.05)。手术组CaN磷酸化显著高于假手术组(P<0.01),缬沙坦组显著低于手术组及PD123319组(P<0.05),手术组与PD123319组间差异没有显著性(P>0.05)。结论ucalpain参与激活高压力负荷下心肌组织CaN通路,ucalpain的上调通过AT1起作用,AT1受体拮抗剂的心脏保护作用与其抑制了m-calpain有关。Abstract: ObjectiveTo invesitgate the effect of valsartan on calcineurin signal pathway in hyptertrophied myocardium induced by pressure overloaded in rats.Methods Pressure overloaded model was established by abdominal aorta constriction.Thirty male wistar rats were divided randomly into four groups: sham-operated group, banding group, valsartan group (banding group and valsartan administation), and PD123319 (an AT-2 receptor antagonist) group (banding group and PD123319 administration).Serum and left ventricular myocardium Ang Ⅱ were measured by radioimmunoassays.Protein expression of u-calpain, m-calpain, calcineurin (CaN) and its phosphorylation were measured by immunoprecitipation.ResultsAng Ⅱ concentration in serum and left ventricular myocardium in banding group was higher than that in of sham-operated group, valsartan group, and PD123319 group (P<0.01); Ang Ⅱ concentration in serum in valsartan group was lower than that in of banding and PD123319 groups (P<0.05), but it was higer in left ventricular myocardium tissue (P<0.05).Protein expression of u-calpain and CaN phosphorylation in left ventricular myocardium tissure in banding group was higer than that in of sham-operation group(P<0.01).Valsartan obviously lowered their expressions in banding and PD123319 groups.Conclusion U-calpain is involved in myocardium remodeling in pressure overloaded rat model.The up-regulation of u-calpain is mediated via AT 1 and was reduced by AT 1 receptor antagonists.
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